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ACBI3
- Development stage
- Preclinical
- Lead developer
- Boehringer Ingelheim
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Subcutaneous, Intraperitoneal
01
Overview
ACBI3 is a small-molecule pan-KRAS degrader developed through a collaboration between the University of Dundee and Boehringer Ingelheim. As a heterobifunctional proteolysis-targeting chimera (PROTAC), ACBI3 consists of a ligand that binds to multiple oncogenic KRAS mutants linked to a ligand for the von Hippel-Lindau (VHL) E3 ubiquitin ligase. This recruitment facilitates the polyubiquitination of KRAS proteins, marking them for subsequent degradation by the 26S proteasome. ACBI3 has demonstrated the ability to degrade 13 of the 17 most common KRAS alleles (including G12D, G12V, and G13D) in preclinical models, providing a proof-of-concept for a 'pan-degrader' approach to treat a wide spectrum of KRAS-driven cancers, such as lung, colorectal, and pancreatic malignancies.
- Other names
- pan-KRAS degrader
02
Targets
KRAS (Kirsten rat sarcoma viral oncogene homolog)VHL (Von Hippel–Lindau tumor suppressor protein)
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